Methanesulfonyl-m-anisidine, 4'-(9-acridinylamino)-monohydrochloride (AMSA or Cain's Acridine, NSC 141549) is a promising new anti-tumor drug scheduled for clinical testing. Studies made in our laboratories have shown that AMSA causes a limited, partially reversible fragmentation of the DNA of mouse L1210 leukemia cells as analyzed by alkaline sucrose gradient centrifugation. The proposed research will establish how primary this effect is to the anti-tumor action of AMSA. We feel that it is urgent to determine the extent to which AMSA might also damage DNA of normal tissues and conditions that will minimize such damage to provide guidelines for the use of AMSA in chemotherapy. We propose to characterize metabolites of AMSA and sites on DNA, or other target molecules, that are involved in AMSA action on cells and we will develop methods of general applicability in studying the nucleotide or sequence specific complexing of DNA active drugs.